Recent NCIRS Journal Club summaries
Postlicensure safety surveillance for quadrivalent human papillomavirus
recombinant vaccine.
Slade BA, Leidel L, Vellozzi C, et al.
JAMA. 2009; 302(7): 750-7.
Link
to abstract
Marketing HPV vaccine: implications for adolescent health and
medical professionalism.
Rothman SM, Rothman DJ.
JAMA. 2009; 302(7): 781-6.
Link
to abstract
Slade et al paper: This paper presents VAERS data following over 23 million doses of HPV vaccine having been distributed in the US. The most common reported adverse events were syncope, local reactions, dizziness, nause and headache. Few serious adverse events were identified, including venous thromboembolic events, most of which were in individuals who had another co-existing risk factor, and these are currently being evaluated further. This data provides reassurance as 94% of reports were minor and self-limiting and very relevant for Australian audiences, particularly when clinicians are faced with a patient reporting an adverse event and wondering if this has occurred before. It needs to be emphasised that a report of an adverse event following vaccination, especially months after the vaccine, as in some cases of clots and deaths reported, does not imply causality. A useful summary is found on the CDC website at http://www.cdc.gov/vaccinesafety/vaers/gardasil.htm
Rothman et al paper: This paper reports on the marketing of HPV vaccine and the manufacturer's decision to promote it first and foremost as a means to prevent cervical cancer, rather than HPV infection. It also reports on the use of professional medical associations as "tools" in the marketing. It reviews the educational materials developed by these associations along with pharmaceutical companies and suggest that they were biased and designed to maximise sales and as advocacy tools. It is an interesting paper, worth a read, but does omit some details, including information on how the associations were funded. The advertising and promotional environment in the US is very different to Australia.
The combination of this paper with the VAERS report and accompanying editorial in the one edition of JAMA is designed to capture readers' attention.
Presented by Dr Nick Wood, Clinical Research Fellow, NCIRS
Kinetics of pertussis immune response to tetanus-diphtheria-acellular
pertussis vaccine in health care personnel: implications for outbreak
control
Kirkland KB, Talbot EA, Decker MD, Edwards KM Clinical Infectious Diseases 2009; 49(4): 584-7.
Editorial commentary: Bordetella pertussis booster vaccination for health care personnel immediately following a pertussis outbreak in a hospital?
Birkebaek NH.
Clinical Infectious Diseases 2009; 49(4): 588-90.
Pertussis outbreaks among health care personnel pose substantial risk to patients, especially infants. In adults, prevention through vaccination of health care personnel remains an attractive option. Also, vaccination of health care personnel particularly protects vulnerable infants and elderly from the risk of nosocomial pertussis. The aim of this brief report was to assess the kinetics of humoral immune response to pertussis antigens following vaccination of health care personnel (physicians, staff and volunteers) with adult tetanus-diphtheria-acellular pertussis vaccine (dTpa). One hundred and fifteen asymptomatic participants were recruited with median age of 45 years (range 19–79 years) and serum samples were collected before vaccination and at 1, 2 and 4 weeks post vaccination. All participants were asked if they experienced any respiratory illness during or after the study. Approximately 50% of the subjects demonstrated antibody response to all pertussis antigens at 1 week post-vaccination, >87% demonstrated antibody response to all pertussis antigens at 2 weeks post vaccination. Antibody responses at 2 and 4 weeks were nearly the same for all antigens. Results suggest early dTpa may be valuable to prevent illness and transmission among adults in pertussis outbreak settings.
Editorial commentary: Discussed brief limitations of the brief report. Firstly, the small sample size and lack of non-vaccinated comparative control group thereby decreasing the impact of the study. Secondly, confirmation of cases by PCR or culture would be worth consideration in future studies.
Presented by Mamta Porwal, Research Officer, NCIRS
Invasive Haemophilus influenzae infections in Germany: impact of non-type b serotypes in the post-vaccine era.
Kalies H, Siedler A, Grondahl B, Grote V, Milde-Busch, von Kries R. BMC Infectious Diseases 2009; 9: 45.
This paper describes the epidemiology of invasive Haemophilus influenzae (Hi) disease caused by both capsulated and non-capsulated strains in children under 10 years of age during 8 years (1998–2005) of active surveillance in the post Haemophilus influenzae b (Hib) conjugate vaccine era in Germany. The study aims in particular to assess a potential shift towards more capsulated non-b and non-capsulated Hi (grouped together as non-type b Hi strains) invasive infections in a backdrop of high Hib vaccine coverage. A similar study among Canadian children reported an increase in the annual average incidence of invasive disease due to non-type b Hi strains during a 6-year period (1996–2001) in the era of universal vaccination against Hib. The proportion of cases of invasive Hi disease caused by non-type b strains was 51% in this study compared to 60% in the Canadian study. The serotype causing the highest proportion of capsulated non-type b Hi infections was ‘f’ among German children, whereas it was serotype ‘a’ in Canadian children. Seven out of 64 Hib cases reported in this study had received a complete course of either PRP-OMP or PRP-T conjugate Hib vaccine prior to disease onset. Morbidity and mortality due to invasive non-type b Hi infections was greater than invasive Hib infections. Detailed information on the epidemiology of non-type b invasive Hi disease in Australia in the post Hib vaccination era is not available for comparison. Together with Hib carriage rates it would be useful to monitor the patterns of non-type b invasive Hi disease occurrence to understand the full impact of Hib conjugate vaccines.
Additional reading
McConnell A, Tan B, Scheifele D, Halperin S, Vaudry W, Law B, Embree J. Invasive infections caused by Haemophilus influenzae serotypes in twelve Canadian IMPACT centres, 1996–2001. Pediatric Infectious Disease Journal 2007; 26:1025-1031
Presented by Dr Sanjay Jayasinghe, Senior Policy Officer, NCIRS
Socioeconomic impact of influenza on healthy children and their families.
Principi N, Esposito S, Marchisio P, Gasparini R, Crovari P.
Pediatric Infectious Diseases Journal. 2003; 22(10 Suppl): S207-10.
The findings of this Italian study are very relevant to Australia at
this point of time, especially considering the impact of swine flu among
young children. While scientists and the community are
extremely concerned about the clinical implications of swine flu, researchers
should also bear in mind that children and their household contacts can
be affected severely in terms of quality of life, and lost school or work
days. This study demonstrated that children with influenza tend to have
longer durations of fever and absenteeism from day care or school when
compared with those without influenza (p<0.0001). The household contacts
of children with influenza also had more medical visits, missed work or
school days, and the need for help at home to take care of sick children
(p<0.0001). Having seen the significant socioeconomic impact brought
by influenza to families, the authors emphasised the need to introduce
programs to vaccinate children in order to protect the children themselves,
as well as their household contacts. They also suggested that economic
modelling of influenza immunisation programs should be done.
Presented by Maria Chow, Research Assistant, NCIRS
Seize the moments: missed opportunities to immunize at the family practice level.
Turner N, Grant C, Goodyear-Smith F, Petousis-Harris H.
Family Practice 2009; 26(4): 275–8.
Missed opportunities (MOs) are an important factor contributing to incomplete immunisation. This study described the frequency and characteristics of MOs within a New Zealand primary health care setting and estimated their effect on incomplete immunisation. It involved an audit of medical records of randomly selected children aged less than 2 years from 62 practices in Auckland, New Zealand. The study found that MOs occurred in 97% of practices. The MOs were more common with acute illness visits and contraindications for immunisation were present in 5% of visits. In addition, children with MO visits were 3 times more likely to be incompletely immunised. This audit concluded that MOs to vaccinate children occurred in most practices and that directives should focus on the practitioner and the practice system to reduce MOs.
Presented by Dr Aditi Dey , Epidemiologist, NCIRS
On Thursday 16th July 2009, Prof Margaret Stanley, from the Department of Pathology at the University of Cambridge presented to NCIRS on “Immuno-biology of HPV infection and how HPV vaccines work”. Key highlights are summarised below.
Human papillomaviruses
Human papillomaviruses (HPV) are small DNA viruses that are species specific
and epitheliotropic. More than 100 HPV types have been cloned and characterised
from clinical biopsies of cutaneous or mucosal surfaces.
About 30 to 40 HPV types infect the anogenital tract of both men and women. In these sites the viruses fall into two groups: low risk viruses such as HPV 6 and HPV 11 that cause genital warts and recurrent respiratory papillomatosis, as well as contributing to low grade cervical, vaginal and vulval lesions; and high risk HPVs which are associated with anogenital cancers. There are ~15 oncogenic HPV types, the most important of which are HPV 16 and HPV 18, causing ~70% of cervical cancers worldwide.
Natural history of infection
After infection there is a latent period between infection and HPV DNA
detection. This interval is of variable duration extending for weeks,
months or even years and is probably related to the dose of infectious
virus.
Eventually the virus is kick started into action, virus replication is initiated, viral DNA can be detected in cervical swabs or genital skin scrapes and clinical lesions become evident. Cycles of virus replication, assembly and shedding, apparently in the absence of an immune response, then continue for a variable period that may extend for at least 12–18 months for the high risk HPV types. but Eventually a cell mediated immune (CMI) response is initiated with cytotoxic effectors accompanied or followed by seroconversion and antibody to the major coat protein of the virus L1. The vast majority of infected individuals – 80–90% of women – make a good CMI response, they become HPV DNA negative and in general remain refractory to re-infection by the HPV type against which they have mounted a successful immune response. A minority of women, 10–20%, make an inadequate CMI response and remain DNA positive with persistent virus infection. This group of women are at risk for progression to high grade cervical, vulval and vaginal intra-epithelial neoplasia (CIN2/3, VIN3, VaIN3), and therefore invasive cancers, at these sites.
HPV antibodies
In natural infections, neutralising antibodies are type specific. The
average time to seroconversion for HPV 16 infections is 8–9 months
after the first detection of HPV DNA and apparently only 50–70%
of women with incident infection seroconvert. Peak serum antibody concentrations
are low but at least 25% of women continue to have detectable antibody
over a 10 year period post seroconversion. Nonetheless evidence from animal
infections show that this neutralising antibody is protective and passive
immunisation experiments in dogs, with purified immunoglobulin G from
animals post wart regression, demonstrate that the immunised animals are
protected against viral challenge and disease.
It is important to note that HPV serology is not standardised and there is no immune correlate of protection for HPV antibodies.
Prophylactic HPV vaccines
Prophylactic HPV vaccines are sub unit protein vaccines comprised of the
L1 coat protein assembled into virus like particles (VLPs). VLPs are empty
protein shells almost identical to the virus particle. Passive immunisation
experiments using the dog and rabbit models showed that the antibodies
generated after VLP immunisation protected against viral challenge and
wart formation.
Extensive clinical trials have served to confirm the efficacy, immunogenicity and safety of HPV vaccines.
While the passive transport of serum antibodies into the squamo-columnar junction of the cervix could explain the mode of action of VLP antibodies, this would not explain protection at keratinised surfaces of the vulva, penis and peri-anal skin. Recent studies have shown that HPV infection requires micro abrasion of squamous epithelium that results in epithelial denudation but retention of basement membrane. The microwound would result in an immediate serous exudate rich in plasma proteins including serum IgG, phagocytes, and immunocytes including memory B cells. Virus neutralisation and a recall response would ensue.
Studies have also examined the proposed mechanism of virus entry. HPV
initially binds by a primary receptor to this exposed basement membrane
before entry to keratinocytes. This is a protracted process extending
over 24–48 hours during which virus capsid undergoes conformational
change. The mechanism by which neutralising antibodies to HPV prevent
viral entry is via binding to capsid, and preventing basement membrane
attachment and the conformational distortion which is essential for successful
entry. These antibodies neutralise at extremely low concentrations –
10 -12M
Duration of Protection
Human subjects involved in an extension study with the quadrivalent
HPV vaccine demonstrated immune memory when given an antigen challenge
5 years after the vaccination course. This is reassuring but needs to
be supplemented with long term follow up of vaccinated cohorts.
Further reading
Stanley M. Immunobiology of HPV and HPV Vaccines. Gynecologic Oncology
2008;109:S15-S21
The effect of 23-valent pneumococcal polysaccharide vaccine on
immunological priming induced by 7-valent conjugate vaccine in asplenic
subjects with beta-thalassemia.
Orthopoulos GV, Theodoridou MC, Ladis VA, Tsousis DK, et al.
Vaccine 2009;27(3):350-4.
Link
to abstract
This is the first study to evaluate the effect of 23-valent pneumococcal
polysaccharide vaccine (PPV) on 7-valent pneumococcal conjugate vaccine
(PCV)-induced immunological priming in splenectomised patients with ß-thalassemia.
The results suggest that one dose of PPV following PCV does not affect
PCV priming in splenectomised subjects with ß-thalassemia which
is congruent with the fact that combined PCV/PPV schedules have been recommended
for subjects with sickle cell disease and HIV infection. However, combined
schedules should not be used for those already vaccinated with multiple
PPVs prior to PCV, in order to avoid further overloading with polysaccharide
antigens that cause hyporesponsiveness; repeated PPV immunisations are
required to maintain the benefit of extended protection but the biological
significance of hyporesponsiveness induced by such practice is not clear
so far. There is an urgent need for the new generation of pneumococcal
vaccines offering long-lasting protection against most pathogenic serotypes
for better protection of high risk individuals.
Presented by Dr Deepika Mahajan, Research Officer, NCIRS
Do they accept compulsory vaccination? Awareness, attitudes and
behaviour of hospital health care workers following a new vaccination
directive.
Seale H, Leask J, MacIntyre CR.
Vaccine 2009;27(23):3022-5.
Link
to abstract
Achieving high vaccination rates among health care workers (HCW) is an
ongoing challenge. In 2007, the state of New South Wales, Australia, instituted
a policy directive with compulsory provisions for health care workers
to be vaccinated. This study sought to identify staff awareness and attitudes
in the early phase of implementation. It involved a self-completed paper-based
or electronic survey of HCWs in two tertiary referral teaching hospitals
in Sydney, Australia, in 2007. A total of 894/1200 completed the paper
survey, while a further 185 completed it online. Of the 1079 respondents,
60% (646/1079) were aware of the policy directive but only 10% (63/646)
described the specific requirements. Seventy-eight per cent supported
the policy; 13% neither supported nor opposed it; and 4% opposed it. This
survey provides an early, broad indication of the level of understanding
and the attitudes of the HCWs towards the new directive.
Presented by Dr Holly Seale, Associate Lecturer, School of Public
Health and Community Medicine, UNSW
Papanicolaou screening behavior in mothers and human papillomavirus
vaccine uptake in adolescent girls.
Chao C, Slezak JM, Coleman KJ, Jacobsen SJ.
American Journal of Public Health 2009;99(6):1137-42.
Link
to abstract
As this is one of the first papers to measure determinants of actual uptake of HPV vaccine (as opposed to acceptance of HPV vaccine), the results are very exciting. The research found that a mother's past history of Pap screening was associated with both her daughter's initiation and completion of HPV vaccination. The authors took this to mean that a preventive ideology was associated with HPV vaccination. However, attitudes were not measured directly. The interpretation may be correct, but the researchers may also have been measuring how likely women are to comply with medical recommendations. Either way, the research is new and interesting and provides ideas for future directions for the Australian Pap and HPV vaccination registries.
Presented by Dr Spring Cooper, Senior Research Officer, NCIRS
Topic: New products for old diseases. How much are we really spending?
Presenter: Dr Mary Moran, Director, Health Policy Division from the George
Institute for International Health
The George Institute’s Health Policy Division (HPD) focuses on
research and development (R&D) of new products for neglected diseases
with a view to support donors and policy-makers to make better and more
cost-effective decisions.
The diseases that are largely focused on are ‘neglected diseases’
Type III (e.g. rotavirus, leprosy) which are overwhelmingly or exclusively
incident in the developing countries, and Type II (e.g. HIV/AIDS, tuberculosis
[TB]) which occur in both rich and poor countries, but with a substantial
proportion of the cases in the poor countries.
Research and development funding data only exists for three of the neglected
diseases: AIDS, TB and malaria. There has, however, been a dramatic increase
in funding for research and development through:
– Philanthropic funders
– Increased government investment
– New Product Development Partnerships (PDPs)
– Increased industry activity (partnership approach)
This is relevant to Australia as neglected tropical diseases are also
a domestic issue in terms of recent dengue outbreaks in Northern Queensland,
and rheumatic fever, trachoma and leprosy affecting Indigenous communities.
Australian research institutes and companies are involved in developing
new neglected disease products which are making significant impacts.
G-FINDER 2008 is a survey conducted by the HPD of global investment into Research and Development of new products for neglected diseases.
G-FINDER surveyed 134 funders in 43 countries for their 2007 R&D investment into: 30 neglected diseases; 127 product areas for these diseases, including drugs, vaccines, diagnostics, microbicides, vector control products and platform technologies; all types of product-related R&D, including basic research, discovery and preclinical, clinical development, Phase IV and pharmacovigilance studies; and baseline epidemiological studies.
Just over $2.5 billion was invested into R&D of new neglected disease products in 2007, with HIV/AIDS, TB and malaria receiving nearly 80% of this amount.
It is clear that the participation of so many organisations and countries
in the development of new neglected disease products is a remarkable and
welcome change from past decades of inertia and neglect. However, most
diseases are still not receiving enough money to make one product.
In summary, an expansion of funding efforts so all those that can, will
contribute, and all diseases receive the attention they deserve, would
lead to a dramatic positive impact on the health of developing country
patients afflicted with these diseases.
A detailed report on the G-Finder 2008 can be viewed online HERE
Brief review of the 1976 Swine Flu outbreak in the US
During the winter of 1976, there was an explosive outbreak of respiratory
illness among recruits returning to Fort Dix following their Christmas/New
Year furlough. It became apparent that there were 2 strains of influenza
circulating amongst the recruits - a "seasonal" H3N2 and an
unidentified influenza virus. One soldier died and tracheal swabs also
revealed this "new" influenza virus. A little later it was determined
that this was indeed influenza but was a swine infleunza virus named as
Hsw1N1. No cases of Hsw1N1 were ever detected in the civilian population
outside of Fort Dix and it was reported that in total between January
and February 1976, 230 soldiers had been infected with one death reported.
In light of the previous pandemics in 1957 and 1968 a decision was made to produce a monovalent H1N1 influenza vaccine and 40-45 million doses of this vaccine were administered to the US adult population between late October and December 1976. There were no cases of Hsw1N1 ever isolated outside of the Fort Dix cases that had occurred in Jan-Feb 1976.
In the beginning of December 1976, 2 clusters totalling 7 cases of Guillian-Barre syndrome (GBS) were reported following vaccination with the monovalent swine influenza vaccine. The decision was made to suspend the vaccination program immediately on December 16, 1976. Surveillance to detect cases of GBS, including those following swine influenza vaccine, was instituted and a total of 1098 cases of GBS were reported between October 1 1976 and January 31 1976. It was found that there was an excess of cases of GBS following vaccination.
During the course of persons seeking compensation through the US legal system as a result of having complications following receiving the 1976 swine flu vaccine, a Judge ordered a review of the surveillance data for GBS cases and other relevant documents and files from the CDC from during this period. This lead to a review of 1300 cases of GBS and the reclassification of cases into either extensive or limited motor involvement. The relative risk for acquiring GBS in the 6 weeks following receiving the 1976 swine flu vaccine was found to range from 3.96 to 7.75 depending on the baseline estimate of normal or endemic GBS chosen. This equated to 4.9 to 5.9 cases of GBS per million doses of swine influenza vaccine. GBS notifications were found to have retuned to baseline very shortly after cessation of the vaccine program.
GBS has rarely been reported following administration of routine seasonal
influenza vaccine.
Suggested readings re the 1976 Swine Influenza outbreak:
Guillain-Barre
syndrome following vaccination in the National Influenza Immunization
Program, United States, 1976--1977.
Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ, Keenlyside RA, Ziegler
DW, Retailliau HF, Eddins DL, Bryan JA. Am J Epidemiol. 1979 Aug;110(2):105-23.
PMID: 463869 [PubMed - indexed for MEDLINE]
Guillain-Barré
syndrome and its relationship to swine influenza vaccination in Michigan,
1976-1977.
Breman JG, Hayner NS. Am J Epidemiol. 1984 Jun;119(6):880-9. PMID: 6731430
[PubMed - indexed for MEDLINE]
Langmuir AD, Bregman DJ, Kurland LT, Nathanson N, Victor M. Am J Epidemiol.
1984 Jun;119(6):841-79. PMID: 6328974 [PubMed - indexed for MEDLINE]
Reflections
on the 1976 swine flu vaccination program.
Sencer DJ, Millar JD. Emerg Infect Dis. 2006 Jan;12(1):29-33. PMID: 16494713
[PubMed - indexed for MEDLINE]
Swine
influenza a outbreak, Fort Dix, New Jersey, 1976.
Gaydos JC, Top FH Jr, Hodder RA, Russell PK. Emerg Infect Dis. 2006 Jan;12(1):23-8.
PMID: 16494712 [PubMed - indexed for MEDLINE]
Presented by Dr Jane Jelfs, Manager Policy Support, NCIRS
Novel Influenza A (H1N1) Virus Infections in Three Pregnant Women
— United States, April–May 2009
Centers for Disease Control and Prevention (CDC)
MMWR 2009;58:497–500
Link to
article
CDC first identified cases of respiratory infection with a novel influenza
A (H1N1) virus in the United States on April 15 and 17, 2009 (1). During
seasonal influenza epidemics and previous pandemics, pregnant women have
been at increased risk for complications related to influenza infection
(2–5). In addition, maternal influenza virus infection and accompanying
hyperthermia place fetuses at risk for complications such as birth defects
and preterm birth (6). As part of surveillance for infection with the
novel influenza A (H1N1) virus, CDC initiated surveillance for pregnant
women who were infected with the novel virus. As of May 10, a total of
20 cases of novel influenza A (H1N1) virus infection had been reported
among pregnant women in the United States, including 15 confirmed cases
and five probable cases.
CDC Recommendations
1. Pregnant women in close contacts with confirmed/probably/suspected
cases • Prophylaxis for 10 days
2. Pregnant cases (confirmed/probably/suspected) • Treatment for
5 days
3. Oseltamivir is preferred for pregnancy women because of systemic absorption
4. Theoretically, higher systemic absorption might suppress influenza
viral loads more effectively in sites other than the respiratory system
(e.g., placenta) and might provide better protection against mother-child
transmission
References
1. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence
of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med
2009;361. [E-pub ahead of print].
2. Dodds L, McNeil SA, Fell DB, et al. Impact of influenza exposure on
rates of hospital admissions and physician visits because of respiratory
illness among pregnant women. CMAJ 2007;176:463–8.
3. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza
on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol
1998;148:1094–102.
4. Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy.
Am J Obstet Gynecol 1959;78:1172–5.
5. Harris JW. Influenza occurring in pregnant women. JAMA 1919;72:978–80.
6. Rasmussen SA, Jamieson DJ, Bresee JS. Pandemic influenza and pregnant
women. Emerg Infect Dis 2008;14:95–100.
7. Jamieson DJ, Theiler RN, Rasmussen SA. Emerging infections and pregnancy.
Emerg Infect Dis 2006;12:1638–43.
8. CDC. Prevention and control of influenza: recommendations of the Advisory
Committee on Immunization Practices (ACIP), 2008. MMWR 2008;57(No. RR-7).
9. Freund B, Gravenstein S, Elliott M, Miller I. Zanamivir: a review of
clinical safety. Drug Saf 1999;21:267–81.
10. Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu)
and its potential for use in the event of an influenza pandemic. J Antimicrob
Chemother 2005;55(Suppl 1):i5–21.
Presented by Kevin Yin, Research Assistant, NCIRS
Will they just pack up and leave? Attitudes and intended behavior of hospital health care workers during an influenza pandemic.
Seale H, Leask J, Po K, MacIntyre CR.
BMC Health Services Research 2009;9:30.
Open access article
During a pandemic, health care workers (HCWs) will be essential to the health system response. Pandemic plans often specify that, in addition to patient care, HCWs will be involved in public health education, epidemiological surveillance, quarantine management, fever clinics, staging facility operation, and more. Complicating this, however, are the various conflicting ethical and psychosocial issues relating to HCWs during an influenza pandemic. An understanding of HCW knowledge, attitudes and behaviour is crucial in planning for an influenza pandemic. Addressing these issues is particularly important, as it has been argued that the threat of pandemic influenza may lead to aimless or unreasonable actions by health care workers.
In 2007 we undertook a cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs, to explore their knowledge, attitudes and intended behaviour towards pandemic influenza. The self-administered questionnaire was distributed to hospital personnel in two tertiary-referral teaching hospitals (one adult and one paediatric).
Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n=873) but less than half were able to correctly define it (43.9%, n=473). Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. We identified two issues in this study that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; and secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans.
Presented by Dr Holly Seale, School of Public Health and Community Medicine, UNSW
Providers’ opinions on the use of MMRV vaccine - an unpublished study by Allison Kempe et al from University of Colorado, presented at the U.S. Advisory Committee on Immunization Practices (ACIP) meeting in February 2009
This was a survey of US providers regarding MMRV vaccine and febrile seizures.
The context of the survey was preliminary findings of two MMRV vaccine post-licensure studies that children 12-15 months old who received MMRV vaccine had roughly a two-fold increased risk of febrile seizures between 5 and 12 days after vaccination compared to children vaccinated with separate measles, mumps, and rubella (MMR) vaccine and varicella vaccines at the same visit.
These results suggest that, between 5 and 12 days after vaccination, about one additional febrile seizure will occur among every 2,000 children who receive MMRV vaccine instead of separate MMR and varicella vaccines at the same visit. These studies did not assess risk of febrile seizures in children receiving MMRV at 4-6 years of age. In light of these studies, the ACIP in February 2008 removed its preference for MMRV vaccine over separate MMR and varicella vaccines although the decision was left to provider preference.
The study investigated whether US family medicine and paediatric physicians were aware of the above information, level of perceived seriousness of febrile seizures, and whether they would recommend MMRV or MMR+V (separate MMR and varicella vaccines) to parents and what influenced their recommendation.
The authors randomly recruited family medicine (FM) and paediatric physicians (Peds) from existing sentinel networks from October 2008 to January 2009 and 73% responded (620/849).
Most FM were unaware of the increased risk of febrile seizures associated with MMRV and change in ACIP recommendations, whereas most Peds were aware of both. FM were more likely than Peds to feel that febrile seizures are very or moderately serious medical events (23% vs. 8%). However, the majority (>90%) of both FM and Peds thought parents perceive febrile seizures as either very or moderately serious events.
Given the above information regarding febrile seizures after MMRV, 9% (FM) and 21% (Peds) intended to give MMRV to healthy 12-15 month olds. Despite lack of data, only 20% (FM) and 38% (Peds) intended to give MMRV to healthy 4-6 year olds. Factors correlated with intended use of MMRV vaccine in 12-15 month olds were potential to improve varicella up-to-date rates and parent preference for fewer injections. Factors correlated with intended use of separate MMR+V vaccine in 12-15 month olds were increased physician concern about febrile seizures and importance of AAP/AAFP recommendations.
Presented by Dr Julie Leask, Manager Social Research, NCIRS
Influenza immunisation of doctors at an Australian tertiary hospital: immunisation rate and factors contributing to uptake.
Kaufman J, Davis J, Krause V.
Communicable Diseases Intelligence December 2008;32(4):443-8.
Link
to abstract
This paper described a survey undertaken in an Australian tertiary hospital in 2007 to establish the rate of influenza vaccine uptake among doctors and factors contributing to uptake. The reported uptake of 28% was low, but comparable to reports from other Australian hospitals. The main factors contributing to not being immunised were being too busy and the vaccine not being offered conveniently. Interestingly, mobile vaccine carts on wards, which have previously been shown to improve uptake of influenza vaccine among nurses, were not considered convenient by this group of doctors. It was suggested that out-of-hours clinics and vaccination at staff meetings might be better for doctors, who are not located within a single ward and are moving around the hospital throughout the day.
Presented by Dr Helen Quinn, Research Fellow, NCIRS
Why young healthy adults should become a target group for the
influenza vaccination: a cardiologist's point of view.
Ciszewski A. Vaccine 2008;26(35):4411-2.
This was a letter which referred to a number of publications including
two recent NCIRS publications:
Newall AT, Wood JG, MacIntyre CR. Influenza-related hospitalisation and
death in Australians aged 50 years and older. Vaccine 2008;26:2135-41
Link to
abstract
Newall AT, Scuffham PA, Kelly H, Harsley S, MacIntyre CR. The cost-effectiveness
of a universal influenza vaccination program for adults aged 50–64
years in Australia. Vaccine 2008;26:2142-53
Link to
abstract
The author of the letter drew readers' attention to the fact that, from a cardiologist’s point of view, persons aged 50-64 years with coronary artery disease (which is usually followed by a respiratory infection) should receive annual influenza vaccination as this can prevent episodes of acute coronary syndrome. Responses to influenza vaccine are, in general, enhanced in younger individuals compared with the elderly so one could anticipate that vaccine efficacy would be high in this age group. However, epidemiological studies which include patients younger than 65 years with cardiovascular disease should also be undertaken so that the degree to which influenza vaccination can positively impact on coronary episodes in younger age groups can be better assessed.
Presented by Swati Ghotane, Research Assistant, NCIRS
Longevity of hepatitis B immunity following infant hepatitis B vaccination and factors affecting responses to booster vaccination.
Nick's presentation was based on a paper by Li-Yu Wang and Hans Hsienhong
Lin. Ethnicity, substance use, and response to booster hepatitis B vaccination
in anti-HBs-seronegative adolescents who had received primary infantile
vaccination. Journal of Hepatology 2007;46(6):1018–1025.
Link to
abstract
Substance use/abuse has been shown to reduce primary responses to hepatitis B vaccine.This is an interesting paper as it reports on reduced responses to booster vaccination in Taiwanese adolescents aged 15 to 18 years. It is of interest locally as the first groups vaccinated in Australia were Indigenous infants and infants born to mothers who came from high hepatitis B endemic countries, and these children are now over 15 years old. In the Taiwanese study approximately 23% failed to respond to a booster dose of hepatitis B vaccine. Follow-up studies of Australian adolescents who were vaccinated in infancy are currently underway.
Presented by Dr Nick Wood, Clinical Fellow, NCIRS
Informing adolescents about human papillomavirus vaccination:
what will parents allow?
Vallely LA, Roberts SA, Kitchener HC, Brabin L.
Vaccine 2008;26(18):2203-10
Link
to abstract
This study evaluated a film that educated students in the UK about HPV and HPV vaccine. The study was well-done, though it would be interesting to determine what happened in the schools as a result of watching the film. The researchers provided information about knowledge and attitudes after watching the film, but we don't know if behaviour was affected. For example, did less girls opt out of receiving the HPV vaccine during the school vaccination day because of the film? The study is highly relevant to the Australian context since Australia has a school-based HPV vaccination program. The AU program doesn't currently provide education directly to girls themselves, though it does provide information sheets for parents/guardians. It is possible that a film, such as the one described in this study, would be a valuable tool for the AU program.
Presented by Dr Spring Cooper, Senior Research Officer, NCIRS
Preliminary literature review regarding reactogenicity and immunogenicity
of adult formulation (low dose antigen content) dTpa administered to children
aged 4-8years
Objective:
Preliminary literature review regarding reactogenicity and immunogenicity
of adult formulation (low dose antigen content) dTpa administered to children
aged 4-8years.
Background:
Firstly, 18-month (4th dose) of DTPa vaccine was dropped in 2003 due to
evidence from trials internationally with long-term sustained protection
(i.e. up to 6 years was achieved following primary immunisation) and secondly,
it was expected that postponing the 4th dose of DTPa until 4 years of
age would reduce extensive local reactions which occurred in 2% of children
following 18-month dose. Hence literature review looking at reactogenicity
and immunogenicity of adult formulation low dose antigen content vaccine
in children aged 4-8years.
Methods:
MEDLINE search from year 2000 to 16/12/2008 was conducted using diphtheria-tetanus-pertussis
vaccines with medical subject headings (MeSH), text and keywords. 301
studies were identified, 18 fulfilled the search terms. Four studies were
eligible for inclusion; nine studies were excluded as they did not meet
the inclusion criteria.
Included papers:
Langley et al (2006) - Level-II - Double blind multi-centre RCT
Scheifele et al (2005) - Level-II - RCT
Marshall et al (2006) - Level-III-2 - prospective cohort
Zepp et al (2007) - Level-III-2 - case-crossover study
Results
Evidence is confounded by differing vaccination schedules and vaccine
formulations used in different countries. Large number of studies identified
were not applicable to Australian context because children were primed
with whole-cell pertussis containing vaccine (which is no longer used
in Australia).
Conclusion
There is limited evidence on lesser reactogenicity/immunogenicity associated
with use of adult formulation low dose (dTpa) vaccine as booster dose
in children aged 4-8years instead of routinely administered DTPa- containing
vaccine.
Included studies
1. Zepp F, Habermehl P, Knuf M, et al. Immunogenicity of reduced antigen
content tetanus-diphtheria-acellular pertussis vaccine in adolescents
as a sixth consecutive dose of acellular pertussis-containing vaccine.
Vaccine 2007;25:5248-52.
2. Scheifele DW, Halperin SA, Ochnio JJ, Ferguson AC, Skowronski DM. A
modified vaccine reduces the rate of large injection site reactions to
the preschool booster dose of diphtheria-tetanus-acellular pertussis vaccine:
results of a randomized, controlled trial.[erratum appears in Pediatr
Infect Dis J. 2006 Mar;25(3):229]. Pediatric Infectious Disease Journal
2005;24:1059-66.
3. Marshall HS, Gold MS, Gent R, et al. Ultrasound examination of extensive
limb swelling reactions after diphtheria-tetanus-acellular pertussis or
reduced-antigen content diphtheria-tetanus-acellular pertussis immunization
in preschool-aged children. Pediatrics 2006;118:1501-9.
4. Langley JM, Predy G, Guasparini R, et al. An adolescent-adult formulation
tetanus and diptheria toxoids adsorbed combined with acellular pertussis
vaccine has comparable immunogenicity but less reactogenicity in children
4-6 years of age than a pediatric formulation acellular pertussis vaccine
and diphtheria and tetanus toxoids adsorbed combined with inactivated
poliomyelitis vaccine. Vaccine 2007;25:1121-5.
Presented by Mamta Porwal, Research Officer, NCIRS
Opportunistic Immunisation of infants admitted to hospital: are
we doing enough?
Ressler KA, Orr K, Bowdler S, Grove S, Best P, Ferson MJ.
Journal of Paediatrics & Child Health 2008;44(6):317-20.
Link
to abstract:
With associated editorial: Minimising missed opportunities to vaccinate.
Crawford NW, Buttery JP. Journal of Paediatrics & Child Health 2008;44(6):315-6.
Ressler et al compared ward-based assessment of immunisation status with ACIR data to determine the effectiveness of opportunistic immunisation of children in the paediatric unit of a large teaching hospital in South Eastern Sydney. 9% of the children included in the study were reported to be not up-to-date with their immunisations according to their hospital charts and poor agreement was reported between ACIR and hospital charts. A missed opportunity to vaccinate was reported in 24% of those identified on admission as overdue but was less likely in those children given a catch-up plan prior to discharge when assessed at 30 and 90 days post-discharge. The study considered the ACIR to be the gold standard when assessing immunisation status but failed to identify the delay associated with reporting to the ACIR. However, the study highlighted the potential of ward-based access to ACIR to reduce inaccuracies of immunisation status and identified areas of potential improvement and strategies to reduced missed opportunities to vaccinate.
Presented by Anita Heywood, Research Assistant, NCIRS, and PhD candidate,
School of Public Health and Community Medicine, The University of New
South Wales
1 December 2008
Brachial plexus neuritis following HPV vaccination
Debeer P, De Munter P, Bruyninckx F, Devlieger R
Vaccine 2008;26(35):4417-9
This is a case report from Belgium of brachial plexus neuritis following
HPV (Gardasil®) vaccination. A 19-year-old student was referred to
the orthopaedic department with a three month history of severe shoulder
pain heavily interfering with normal daily activities after the second
dose of HPV vaccination. Conservative treatment consisting of adequate
analgesia was initiated. Eight months after the onset of the pain, there
was marked improvement of strength and mobility of the left shoulder but
pain remained present requiring high doses of analgesics.
This first case warrants careful attention in view of the large vaccination
campaigns in young adolescents being launched all over the world. The
post-vaccination event described in this patient is one of extreme rarity
and careful monitoring of unusual complications like this is important.
Since the HPV vaccination comprises of three consecutive injections, this
could theoretically potentiate the neurological complications observed
after the first or second injection.
Presented by Dr Aditi Dey, Epidemiologist, NCIRS
24 November 2008
Effects of influenza plus pneumococcal conjugate vaccination versus influenza
vaccination alone in preventing respiratory tract infections in children:
a randomized, double-blind, placebo-controlled trial
Jansen AG, Sanders EA, Hoes AW, van Loon AM, Hak E
Journal of Pediatrics 2008;153(6):764-70
The main objective of this study was to evaluate the effects of influenza
vaccination with or without heptavalent pneumococcal conjugate vaccination
on respiratory tract infections (RTIs) in children.
This study was a randomised, double-blind, placebo-controlled trial conducted
in the Netherlands, comprising 579 children aged 18 to 72 months with
a previous history of physician-diagnosed RTI who had not been vaccinated
with any of the study vaccines, recruited in the months of September and
October in the three years of 2003, 2004 and 2005. Children with specific
medical conditions for which the influenza or pneumococcal vaccine were
recommended were excluded. The participating children were randomly assigned
to one of the three groups, to receive either 2 doses of parenteral inactivated
trivalent subunit influenza plus heptavalent pneumococcal conjugate vaccination
(TIV+PCV7), influenza plus placebo vaccination (TIV+plac), or control
hepatitis B virus vaccination plus placebo (HBV+plac).
Study results showed that during the influenza seasons, febrile RTI were
reduced by 24% (95% confidence interval [CI] 1% to 42%) in the TIV+PCV7
group and by 13% (95% CI
-12% to 32%) in the TIV+plac group compared with the control group. The
occurrence of PCR-confirmed influenza was reduced by 52% (95% CI 7% to
75%) in the TIV+PCV7 group and by 51% (95% CI 3% to 75%) in the TIV+plac
group. Episodes of AOM were reduced by 57% (95% CI 6% to 80%) in the TIV+PCV7
group and by 71% (95% CI 30% to 88%) in the TIV+plac group. There were
no significant differences in primary care visits and antibiotic prescriptions
among the three groups. Outside of the influenza seasons, no significant
effects of vaccinations were demonstrated on the studied outcomes. Two
of the three influenza seasons were mild seasons, and the influenza vaccine
virus strains were suboptimal matches with the dominant circulating influenza
strains over all the three seasons.
Results of this study were in agreement with other published non-randomised,
unblinded or small studies or the few meta-analyses on the effect of the
inactivated influenza vaccine in younger children. This study had limited
power to detect a small additional benefit, if any, of the pneumococcal
conjugate vaccine against AOM in children of this age group.
Presented by Dr Clayton Chiu, Clinical Research Fellow,
NCIRS
3 November 2008
Too little but not too late: results of a literature review to
improve routine immunization programs in developing countries
Rymen TK, Dietz V, Cairns KL
BMC Health Services Research 2008;8:134
This review provides a valuable insight into the status of immunisation
related health services research in developing countries.
A disproportionately high burden of vaccine preventable diseases is borne
by low and middle income countries due to their failure to achieve acceptable
levels of vaccine coverage. Against this backdrop, the authors claim that
there is a clear need to make national and sub-national level managers
of immunisation services in these countries aware of proven strategies
designed to strengthen routine immunisation programs at community and
facility level to improve vaccine coverage.
However, the key message that emerges from this review is that there is
a disturbing lack of good quality research based evidence related to immunisation
services to inform policy and practice in developing countries.
The authors have conducted a comprehensive search of the published and
grey literature. They used a standardised assessment tool, comprising
elements considered critical to the scientific quality of a study and
the readability to understand adequately an intervention and its impact,
to rate papers. The authors compiled four approaches for immunisation
service managers to identify effective strategies: bringing immunisation
closer to the community, using information dissemination to increase demand
for vaccination, changing practices in fixed sites and using innovative
management practices.
Despite an exhaustive search, the authors have been able to identify only
25 papers for the period from 1974 to 2004 that meet the inclusion criteria
for the review. They were only from 17 separate countries and 3 were situation
specific with limited transferability. Papers were also found to be of
moderate scientific quality probably because research was not the primary
purpose of the activity described. There were only 4 papers in the last
10 years. Due to this lack of high quality research based evidence to
inform policy and practice these countries will continue to struggle to
make best use of their limited resources. These countries will continue
to be reservoirs of diseases to the rest of the world and their low levels
of vaccine coverage will significantly impact the potential to eliminate
and eradicate vaccine preventable diseases.
Presented by Sanjay Jayasinghe, Senior Project Officer, NCIRS
18 August 2008
World wide experience with inactivated poliovirus vaccine
Bonnet MC, Dutta A
Vaccine In Press, Available online 3 August 2008
This article provides an excellent overview of the development and implementation
of poliomyelitis vaccines and will be an extremely useful reference for
anyone reviewing the global use of these vaccines.
The paper provides an overview of the disease and polioviruses and the
key milestones in the development of a suitable polio vaccine for global
use. The various schedules used by different countries are described with
some countries using inactivated poliomyelitis virus vaccine (IPV) alone,
others using a combination of oral poliomyelitis virus vaccine (OPV) with
some doses of IPV, and some countries continuing to use OPV exclusively.
The authors suggest that IPV could replace OPV due to the high immunogenicity
and safety of IPV and acknowledge the contribution that OPV has made towards
the ultimate aim of the global elimination of polio. A move to IPV will
be necessary to ensure eradication of both wild-type and vaccine-derived
polioviruses as part of the WHO Polio Eradication Initiative.
However, the authors concede that such a move to IPV will be driven by
not only medical but political, ethical, economical and logistical considerations.
Outer membrane vesicles as acellular vaccine against pertussis
Roberts R, Moreno G, Bottero D, Gaillard ME, Fingermann M, Graieb A, Rumbo
M, Hozbor D
Vaccine 2008;26(36):4639-46
The authors describe a series of experiments undertaken using the animal
mouse-model and an outer membrane vesicle (OMV) vaccine prepared from
2 different B.pertussis strains. Analysis of the proteome of the B.pertussis
OMV indicated that at least 43 potential antigens could be used to develop
an effective pertussis vaccine although the immune response generated
for each antigen was not assessed individually by the authors. The OMV
included a number of antigens already used in the currently available
acellular pertussis vaccines and the use of surface exposed protein such
as those described allow for a preferentially targeted immune response.
However, this OMV study was limited to use in an animal model at present.
OMV vaccines have already been described for other micro-organisms, such
as Neisseria.
Presented by Dr Jane Jelfs, Immunisation Handbook and Policy Coordinator,
NCIRS